To combat novel emerging infectious diseases, drug-resistant organisms, and potential weaponized biological threats, the identification of new therapeutic targets, and the development of drugs exploiting those targets, is essential. The Assay Core is a key component of the Antiviral Drug Discovery and Development Center (AD3C), contributing to the goals of each of the individual Research Projects and to the Medicinal Chemistry Lead Development Core (MCLDC). The overarching goal of the Assay Core is to assist the MCLDC to optimize compounds into drugs by providing biological screening support. As part of the current AD3C CETR program, the Assay Core (designated as the Screening Core in the current CETR program), conducted seven HTS campaigns to identify compounds with antiviral activity against each of seven emerging pathogen studied in this proposal. The compounds identified by HTS for each virus have been developed into leads by the MCLDC. As a continuation of this effort in the current CETR proposal, the Assay Core will provide the testing data needed to develop structure activity relationships (SAR) for further optimization of these leads. Having an assay core with at least medium-throughput capacity is essential to meet the goal to discover compounds with the appropriate drug-like characteristics to enter animal studies. The resulting data for each compound tested by the Assay Core will be maintained in a centralized database with easy access by the members of the MCLDC and the Research Project teams. The Assay Core will work with key members of the MCLDC and Research Project teams to make decisions for compound progression. The end result of this process will be the identification of novel compounds appropriate for in vivo testing and IND-enabling studies.